PXD032370

PXD032370 is an original dataset announced via ProteomeXchange.

Title	Dual CBS and MPST gene knockdown induces inflammation and impairs adipogenesis in human adipocytes
Description	Recents studies in mice and humans demonstrated the relevance of H2S-synthesising enzymes (such as CTH, CBS and MPST) in adipose tissue physiology and preadipocyte differentiation into adipocytes. Here, we aimed to investigate the combined role of CTH, CBS and MPST in the preservation of adipocyte protein persulfidation and adipogenesis. Joint CTH, CBS and MPST gene knockdown was achieved treating fully human adipocytes with siRNAs against these transcripts (siRNA_MIX). Adipocyte protein persulfidation was analyzed by a mass spectrometry label-free quantitative approach coupled with a dimedone-switch method for protein labeling and purification. The proteomic analysis quantified 216 proteins with statistically different persulfidation levels in KD cells compared to control adipocytes. In fully differentiated adipocytes, CBS and MPST mRNA and protein levels were abundant, whereas CTH expression was very low. Of note, siRNA_MIX administration resulted in a significant decrease in CBS and MPST expression, without impacting on CTH. Dual CBS and MPST gene knockdown resulted in decreased expression of relevant genes for adipocyte biology, including adipogenesis, mitochondrial biogenesis and lipogenesis, but increased proinflammatory- and senescence-related genes, in parallel to a significant disruption in adipocyte protein persulfidation pattern. While among less persulfidated proteins, we identified several relevant proteins for adipocyte adipogenesis and function, among the most persulfidated, key mediators of adipocyte inflammation and dysfunction, but also some proteins that might have a positive role of adipogenesis were found. In conclusion, current study indicates that joint knockdown of CBS and MPST (but not CTH) in adipocytes impairs adipogenesis and promotes inflammation, possibly by disrupting the pattern of protein persulfidation in these cells, and suggesting that these enzymes were required for the functional maintenance of adipocytes.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-12_00:31:10.923.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD032370
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Mikel Azkargorta
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	sulfated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-17 09:35:22	ID requested
⏵ 1	2022-08-12 00:31:11	announced

Latorre J, Aroca A, Fern, á, ndez-Real JM, Romero LC, Moreno-Navarrete JM, Genes Induces Inflammation, Impairs Adipocyte Function-Related Gene Expression and Disrupts Protein Persulfidation in Human Adipocytes. Antioxidants (Basel), 11(6):(2022) [pubmed]

submitter keyword: Human adipocytes, adipogenesis, inflammation, protein persulfidation.

Felix Elortza
contact affiliation	Proteomics Platform CIC bioGUNE Bizkaia Tech. Park Build. 800 Derio 48160 Spain
contact email	felortza@cicbiogune.es
lab head
Mikel Azkargorta
contact affiliation	Proteomics Platform CIC bioGUNE
contact email	mazkargorta@cicbiogune.es
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD032370
     1. Label: PRIDE project
     2. Name: Dual CBS and MPST gene knockdown induces inflammation and impairs adipogenesis in human adipocytes